Comparison of antagonist activity of spantide family at human neurokinin receptors measured by aequorin luminescence-based functional calcium assay
Comparison of antagonist activity of spantide family at human neurokinin receptors measured by aequorin luminescence-based functional calcium assay
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DOI：
10.1016/j.regpep.2005.05.006
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发表时间：
2005-11-15
影响因子：
--
通讯作者：
Vanden Broeck, J
中科院分区：
文献类型：
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作者：
Janecka, A;Poels, J;Vanden Broeck, J
神经激肽受体（NK 1、NK 2、NK 3）是G蛋白偶联受体，其在被肽激动剂激活后诱导细胞内钙浓度的瞬时增加。基于由受体介导的Ca 2+水平变化触发的水母发光蛋白衍生的发光的功能测定用于比较Spantides I-III分别对SP-、NKA-和NKB-刺激的NK 1、NK 2和NK 3受体的作用。在研究中使用表达神经激肽受体和脱辅基水母发光蛋白的重组细胞系。所获得的结果表明，所有三个spantides作为竞争性拮抗剂在NK 1和NK 2受体和抑制激动剂诱导的钙反应。对NK 1受体的拮抗作用顺序为spantide II > spantide III > spantide I，对NK 2受体的拮抗作用顺序为spantide III > spantide II > spantide I。所有三种Spantides均未能拮抗NKB诱导的NK 3受体的钙反应。(c)2005 Elsevier B. V.保留所有权利。
Neurokinin receptors (NK1, NK2, NK3) are G-protein-coupled receptors, which upon activation by a peptide agonist induce a transient increase in the concentration of intracellular calcium. The functional assay based on aequorin-derived luminescence triggered by receptor-mediated changes in Ca2+ levels was used to compare the effect of spantides I-III on SP-, NKA- and NKB-stimulated NK1, NK2 and NK3 receptors, respectively. Recombinant cell lines expressing neurokinin receptors and apoaequorin were used in the study. The obtained results indicate that all three spantides acted as competitive antagonists at the NK1 and NK2 receptors and inhibited agonist-induced calcium responses. The rank order of antagonism at the NK1 receptor was spantide II > spantide III > spantide I and at the NK2 receptor was spantide III > spantide II > spantide I. All three spantides failed to antagonize NKB-induced calcium responses at the NK3 receptor. (c) 2005 Elsevier B.V. All rights reserved.